NITRIC OXIDE PATHWAY
The enzyme nitric oxide synthase (NOS) catalyzes the interaction of L-arginine with molecular oxygen to make L-citrulline and NO. There are three forms of NOS that have been found so far: they constitutively expressed, Neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) (Kleinert, Schwarz & Förstermann, 2003). NO, which is mostly produced by iNOS, can be detrimental and pro-inflammatory in high doses. However, the activities of nitric oxide are mostly influenced by the cellular context, NO concentration (depending on distance from the NO source), and the initial priming of immune cells, rather than the enzymatic source (Guzik, Korbut & Adamek-Guzik, 2003). The brain’s NO levels rise dramatically as a result of vertebral ischemia. This is attributed to increased iNOS expression in reactive astrocytes and neutrophils invading the ischemic brain 6–12 hours after the injury, as well as increased eNOS and nNOS expression in the arteries and parenchyma within an hour of the lesion (Iadecola, 1997; Kader, Frazzini, Solomon & Trifiletti, 1993; Zhang et al., 1994). NO has pro-inflammatory and cytotoxic effects at high doses, but it is known to have anti-inflammatory and vasodilator characteristics under certain situations (Coleman, 2001; Sharma, Al-Omran & Parvathy, 2007). L-arginine treatment during the acute period improved symptoms in people with mitochondrial myopathy, encephalopathy, and stroke-like episodes (Koga et al., 2018). During an inhaled NO experiment, peripheral vascular resistance was lowered in a child with traumatic brain injury, despite no changes in middle cerebral artery blood flow, jugular bulb oxygen saturations, or intracranial pressure (Vavilala, Roberts, Moore, Newell & Lam, 2001). According to the researchers, the NO donor had no effect on cerebral blood flow, cerebral perfusion pressure, or cerebral steal in these people (Willmot, Ghadami, Whysall, Clarke, Wardlaw & Bath, 2006). These disparities in results could explain NO toxicity or insufficient NO exposure, which could be explained by differences in NO concentration. More research is needed to determine the role of NO in SAH, which is currently up for contention.